Elsevier

Vaccine

Volume 27, Issue 7, 11 February 2009, Pages 1062-1066
Vaccine

Booster vaccination of adults with reduced-antigen-content diphtheria, Tetanus and pertussis vaccine: Immunogenicity 5 years post-vaccination

https://doi.org/10.1016/j.vaccine.2008.11.102Get rights and content

Abstract

At 60 months post-vaccination, adults (mean age 45.6 years) randomised to receive combined reduced-antigen-content diphtheria–tetanus and acellular pertussis vaccine (dTpa) versus tetanus–diphtheria (Td) + monovalent acellular pertussis (pa) were seroprotected against diphtheria (≥0.016 IU/mL Vero cell assay) and tetanus (≥0.1 IU/mL ELISA assay) in 94.4% and 96.2%, respectively (dTpa), compared with 93.7% and 90.6% (Td + pa). Anti-FHA, anti-PT and anti-PRN antibodies (≥5 EL.U/mL) were maintained in 100%, 89.5% and 95.0% of dTpa versus 100%, 85.5% and 90.6% of pa vaccine recipients. At 5 years post boosting, antibody levels to diphtheria and tetanus are similar amongst adults receiving a dTpa or dT, and pertussis antibodies remain above pre-booster levels in at least 85%.

Introduction

Routine vaccination against pertussis has been recommended for infants since the 1940s, yet it is only within the last decade, corresponding to availability of acellular pertussis vaccines and reduced-antigen-content formulations, that recommendations for booster vaccination of adolescents and adults against pertussis have been developed. Although pertussis disease rarely results in serious complications, hospitalisation or death in older individuals [1], [2], it nevertheless carries a substantial disease burden and economic cost in this population [1], [2], [3], [4]. Recommendations for pertussis booster vaccination of adolescents and adults have been made with the aim of reducing morbidity and healthcare costs in the older population and reducing pertussis transmission to unprotected or partially protected infants by these older individuals. National authorities in Australia [5], United States [6], Canada [7], France [8], Germany [9], Austria, Finland, Andorra and Luxembourg [10] now provide guidelines for pertussis vaccination in older age groups, and several of these countries provide public, fully funded vaccination programs for adolescents. In Australia, an adolescent pertussis booster program was funded for 15–17 year olds in 2003 [5]. Unfunded recommendations for a single dose of dTpa (combined reduced-antigen-content diphtheria–tetanus-acellular pertussis vaccine) for adults were also made in 2003 for parents of a new baby, adults working with young children, especially in a healthcare setting, and other adults where Td vaccine (adult diphtheria–tetanus vaccine) is indicated (at 50 years of age, and more recently, for primary immunisation of adults) [11]. Expert consensus groups continue to advocate strategies to improve vaccination for adolescents and adults primarily directed at protecting susceptible infants against pertussis disease [12], [13]. However, since the duration of protection afforded by acellular pertussis booster vaccines against pertussis disease remains largely unknown, recommendations for subsequent booster doses are lacking.

This study is part of an ongoing assessment into the long-term persistence of antibodies among adults who participated in a trial comparing a single booster dose of dTpa vaccine with stand-alone pa and Td vaccine [14] at 48 and 60 months following vaccination. These data are important because they provide one of the longest periods of follow-up for adults receiving dTpa worldwide and inform policy development for the control of pertussis in adults.

Section snippets

Subjects

This was an open serological follow-up study (263855/026 and 027) conducted at the Centre for Immunisation Research, The Children's Hospital at Westmead, New South Wales, Australia. The results of the preceding vaccination study and serological follow-up studies at 12, 24 and 36 months after vaccination have been reported previously [14], [15]. Briefly, adults aged 18 years or above were randomised to receive either a single injection of a combined dTpa vaccine or Td vaccine followed by

Study population

Of the 550 subjects enrolled in the initial randomised trial [14], 361 (66%) and 308 (56%) subjects returned at the Month 48 and Month 60 sampling time points, respectively (Table 1). Four subjects (all dTpa recipients) were excluded from the primary analysis of the Month 60 cohort due to large (at least ninefold) increases in anti-tetanus or diphtheria antibody concentrations between Month 48 and Month 60. Increases in antibody concentration of this magnitude were considered indicative of

Discussion

This study of yearly serological follow-up of an adult cohort vaccinated with the combined dTpa compared with commercially available Td (+experimental pa vaccine) shows that, in line with previous predictions based on mathematical modelling [16], the long-term persistence of seroprotective diphtheria and tetanus antibodies is similar, despite the significantly higher anti-tetanus antibody GMCs initially observed in the Td-vaccinated group 1 month after the booster dose [14], [15]. Since

Acknowledgements

The authors thank Dr. Joanne Wolter and Julia Donnelly for assistance in preparation of the manuscript and Gunasekaran Ramakrishnan for additional statistical analyses.

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